γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia.

Luong-Gardiol, N.; Siddiqui, I.; Pizzitola, I.; Jeevan-Raj, B.; Charmoy, M.; Huang, Y.; Irmisch, A.; Curtet, S.; Angelov, G.S.; Danilo, M.; Juilland, M.; Bornhauser, B.; Thome, M.; Hantschel, O.; Chalandon, Y.; Cazzaniga, G.; Bourquin, J.P.; Huelsken, J.; Held, W.

doi:10.1016/j.ccell.2019.03.005

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia.

Détails

Télécharger: Luong Gardiol.pdf (4409.75 [Ko])
Etat: Public
Version: Final published version
Licence: Non spécifiée

ID Serval

serval:BIB_B56A0F7637FF

Type

Article: article d'un périodique ou d'un magazine.

Collection

Publications

Institution

UNIL/CHUV

Titre

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia.

Périodique

Cancer cell

Auteur⸱e⸱s

Luong-Gardiol N., Siddiqui I., Pizzitola I., Jeevan-Raj B., Charmoy M., Huang Y., Irmisch A., Curtet S., Angelov G.S., Danilo M., Juilland M., Bornhauser B., Thome M., Hantschel O., Chalandon Y., Cazzaniga G., Bourquin J.P., Huelsken J., Held W.

ISSN

1878-3686 (Electronic)

ISSN-L

1535-6108

Statut éditorial

Publié

Date de publication

15/04/2019

Peer-reviewed

Oui

Volume

Numéro

Pages

649-663.e10

Langue

anglais

Notes

Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish

Résumé

The BCR-ABL1 fusion protein is the cause of chronic myeloid leukemia (CML) and of a significant fraction of adult-onset B cell acute lymphoblastic leukemia (B-ALL) cases. Using mouse models and patient-derived samples, we identified an essential role for γ-catenin in the initiation and maintenance of BCR-ABL1 + B-ALL but not CML. The selectivity was explained by a partial γ-catenin dependence of MYC expression together with the susceptibility of B-ALL, but not CML, to reduced MYC levels. MYC and γ-catenin enabled B-ALL maintenance by augmenting BIRC5 and enforced BIRC5 expression overcame γ-catenin loss. Since γ-catenin was dispensable for normal hematopoiesis, these lineage- and disease-specific features of canonical Wnt signaling identified a potential therapeutic target for the treatment of BCR-ABL1 + B-ALL.

Mots-clé

Animals, Fusion Proteins, bcr-abl/genetics, Fusion Proteins, bcr-abl/metabolism, Gene Expression Regulation, Leukemic, Humans, K562 Cells, Mice, Inbred NOD, Mice, SCID, Mice, Transgenic, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology, Proto-Oncogene Proteins c-myc/genetics, Proto-Oncogene Proteins c-myc/metabolism, Survivin/genetics, Survivin/metabolism, Wnt Signaling Pathway, beta Catenin/genetics, beta Catenin/metabolism, gamma Catenin/genetics, gamma Catenin/metabolism, B cell acute lymphoblastic leukemia (B-ALL), BCR-ABL1, BIRC5 (Survivin), MYC, chronic myeloid leukemia (CML), junction plakoglobin, β-catenin, γ-catenin

URN

urn:nbn:ch:serval-BIB_B56A0F7637FF3

OAI-PMH

oai:serval.unil.ch:BIB_B56A0F7637FF

DOI

10.1016/j.ccell.2019.03.005

Pubmed

30991025

Web of science

000464931000012

Création de la notice

28/04/2019 15:35